12-49891779-C-T

Variant names:

• chr12-49891779-C-T
• rs17201502
• NM_012306.4:c.435-665G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012306.4(FAIM2):​c.435-665G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 152,086 control chromosomes in the GnomAD database, including 7,054 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.28 (7054 hom., cov: 32)
• Consequence: FAIM2 NM_012306.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.768
• Publications: 12 publications found

Genes affected

FAIM2 (HGNC:17067): (Fas apoptotic inhibitory molecule 2) Involved in regulation of neuron apoptotic process. Acts upstream of or within negative regulation of extrinsic apoptotic signaling pathway via death domain receptors. Located in membrane raft. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.364 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012306.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAIM2	NM_012306.4	MANE Select	c.435-665G>A		intron	N/A	NP_036438.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAIM2	ENST00000320634.8	TSL:1 MANE Select	c.435-665G>A		intron	N/A	ENSP00000321951.3	Q9BWQ8-1
	FAIM2	ENST00000947305.1		c.453-665G>A		intron	N/A	ENSP00000617364.1
	FAIM2	ENST00000947304.1		c.435-665G>A		intron	N/A	ENSP00000617363.1

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42337 AN: 151968 Hom.: 7052 Cov.: 32

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.429

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.463

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.368

Gnomad OTH AF: 0.295

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.278 AC: 42335 AN: 152086 Hom.: 7054 Cov.: 32 AF XY: 0.279 AC XY: 20742 AN XY: 74338

African (AFR) AF: 0.101 AC: 4203 AN: 41508

American (AMR) AF: 0.252 AC: 3849 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.463 AC: 1606 AN: 3472

East Asian (EAS) AF: 0.224 AC: 1155 AN: 5156

South Asian (SAS) AF: 0.325 AC: 1565 AN: 4818

European-Finnish (FIN) AF: 0.365 AC: 3854 AN: 10554

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.368 AC: 25005 AN: 67986

Other (OTH) AF: 0.291 AC: 612 AN: 2106

Alfa AF: 0.347 Hom.: 9171

Bravo AF: 0.258

Asia WGS AF: 0.231 AC: 806 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.4
DANN	Benign	0.70
PhyloP100		-0.77
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs17201502; hg19: chr12-50285562;